Abstract: SA-PO0694
Nivolumab-Induced Membranoproliferative Glomerulonephritis with Nephrotic Syndrome
Session Information
- Glomerular Diseases: Complement-Mediated Glomerulopathies and Infection-Related GN
October 24, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics
Authors
- Mina, Jonathan, Cleveland Clinic, Cleveland, Ohio, United States
- Mehdi, Ali, Cleveland Clinic, Cleveland, Ohio, United States
- Gadegbeku, Crystal A., Cleveland Clinic, Cleveland, Ohio, United States
Introduction
ICI-associated nephrotoxicity typically manifests as ATIN. GN is rare, occurring in around 15% of ICI-nephritis cases, with MPGN representing an uncommon subset. We report nivolumab-induced polyclonal immune complex MPGN with nephrotic syndrome in metastatic melanoma, successfully treated with rituximab.
Case Description
An 86-year-old male with metastatic melanoma developed AKI 1 month after 6th cycle nivolumab monotherapy. Prior ICI exposure included ipilimumab complicated by thrombocytopenia and Sjögren-like syndrome, then T-VEC (a year later), followed by nivolumab monotherapy 4 months later. Baseline Cr was around 1.0 mg/dL. The patient presented with Cr 2.8 mg/dL, UPCR 7.36 mg/mg, hematuria, hypoalbuminemia, and volume overload. Workup (ANA, ANCA, dsDNA, C3, C4, hepatitis panel, HIV) was negative. The patient was admitted for further evaluation. Kidney biopsy showed MPGN with endocapillary hypercellularity and moderate tubulointerstitial fibrosis (36 glomeruli, 2 globally sclerotic). IF demonstrated polyclonal IgG (3+), C3 (3+), C1q (4+), kappa (4+), lambda (4+). EM revealed GBM wrinkling, double contouring, moderate foot process effacement, and abundant subendothelial/mesangial deposits. No evidence of ATIN was identified. Nivolumab was discontinued. The patient received IVMP 1g x3 days followed by oral prednisone taper. He required 2 hospitalizations for volume overload requiring diuresis. At 2-month follow-up: Cr 1.5 mg/dL (eGFR 45), albumin 3.5 g/dL, persistent nephrotic-range proteinuria (24hr 4.8g), ongoing hematuria. Given persistent proteinuria and progressive melanoma, rituximab was initiated (1g IV x2 doses, 2 weeks apart). One month post-rituximab: dramatic improvement with Cr 1.2 mg/dL (eGFR 56) and UPCR 1.0 mg/mg. The patient was successfully tapered off prednisone. ICI rechallenge under consideration.
Discussion
ICI-induced MPGN should be considered in patients developing proteinuria or nephrotic syndrome during ICI therapy. Unlike ATIN which responds to steroids alone, MPGN benefits from B-cell directed therapy. This case demonstrates rituximab's efficacy in achieving rapid steroid-free remission with dramatic proteinuria reduction. Importantly, rituximab may facilitate safe ICI rechallenge, with recent series reporting 75% success without relapse. Early recognition and appropriate treatment are critical to optimize both renal and oncologic outcomes.